`
`UNIVERSITY
`OF SOUTHERN
`CALIFORNIA
`
`Qing Lin, Ph.D.
`Seed IP Law Group, PLLC
`701 Fifth Avenue
`Suite 5400
`
`Seattle, WA 98104
`Eli and Edythe Broad
`Center for Regenerative
`Medicine and Stem Cell
`Research at USC
`
`May 12, 2010
`
`
`
`,
`'
`'
`KCCk SChOOl Of MCdlClI’lC
`University of Southern California
`
`RE: U.S. continuation Patent Application No. 12/541,388
`
`Dear Becky,
`
`l recently learned, via public PAIR, that an amendment was filed in the
`Hope this letter finds you well.
`above case on 24 November 2009, wherein all original claims were canceled, and totally new claims
`were entered. You are listed as the attorney of record in the case.
`
`I am, therefore, providing you with the attached Declaration by me, along with other documents
`(W02009148192 A1, and the International Search Report relating thereto), relating to the above
`application. As an original inventor of this application, I have an ongoing duty of disclosure to the
`USPTO regarding any information material to the patentability of the pending claims, and I think my
`Declaration and accompanying documents therefore need to be considered by the USPTO.
`
`If you would like, I am happy to talk with you about this further.
`
`Sincerely,\
`
`Michael Kahn, Ph.D.
`Provost’s Professor of Medicine and Pharmacy
`Eli and Edythe Broad Center for Regenerative Medicine
`and Stem Cell Research at USC
`Co-Leader Gl Program, Norris Cancer Center
`University of Southern California
`1501 San Pablo, ZNl-533
`Los Angeles, CA 90033
`Phone # 323-442-2063
`Fax # 323-442-4040
`
`E-mail: kahnm@usc.edu
`
`Enclosures: Declaration of Dr. Michael Kahn;
`W02009148192 A1; and the International Search Report relating thereto.
`
`1425 San Pablo Street
`Los Angeles,
`California 90033
`Tel: 323 442 4366
`Fax: 323 442 4040
`http://stemcell.usc.edu/
`
`
`
`
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`‘ Applicants:
`
`Sung Hwan Moon, et al.
`
`Filing Date:
`
`14 August 2009
`
`Serial No.:
`
`12/541,388
`
`For:
`
`REVERSE-TURN MIMETICS AND METHOD RELATING THERETO
`
`Examiner:
`
`Venkataraman Balasubramanian
`
`Art Unit:
`
`1614
`
`10
`
`Commissioner for Patents
`P. O. Box 1450
`
`Alexandria, VA 22313-1450
`
`15
`
`IN SATISFACTION OF DUTY TO DISCLOSE INFORMATION MATERIAL TO
`
`DECLARATION OF DR. MICHAEL KAHN
`
`PATENTABILITY UNDER 37 C.F.R. § 1.56
`
`Sir:
`
`20
`
`I, Dr. Michael Kahn, being duly sworn, say:
`
`1.
`
`I am an original joint
`
`inventor of the above-identified continuation patent
`
`application and very familiar with its originally-filed contents.
`
`I am aware that it discloses and
`
`claims particular novel species and genera of conformationally constrained compounds that mimic
`
`the secondary structure of reverse-tum regions of biologically active peptides and proteins.
`
`25
`
`2.
`
`I am an internationally recognized chemist and scientist and expert in the field of
`
`reverse—turn mimetic structures/scaffolds, and am presently employed as Professor of
`
`Biochemistry and Molecular Biology, Professor of Pharmacology and Pharmaceuticals, and
`
`Provost Professor of Medicine and Pharmacology, 1501 San Pablo, ZNI-533, Los Angeles, CA
`
`90033.
`
`I received a B.A., Chemistry from Columbia University in 1978, and a Ph.D., Chemistry
`
`30
`
`from Yale University in 1983.
`
`I am also a cofounder and outside board member of Prism
`
`BioLabs corporation of Yokohama, Japan.
`
`
`
`3.
`
`I am an author or co-author of 89 peer-reviewed research articles, 11 book
`
`chapters, and an inventor on over 60 patents and patent applications (including the present
`
`application) (APPENDICES B and C), and my research has been presented at numerous national
`
`and international meetings. Many of these presentations have been given at the request of
`conference organizers for both educational workshops on discovery and development of reverse-
`
`turn mimetics and/or the results of my research. My curriculum Vitae is attached hereto as
`
`APPENDIX A.
`
`4.
`
`In my capacity as a Ph.D. level chemist and scientist, I am familiar with a broad
`
`spectrum of organic reverse—turn mimetic structures, and synthetic methods for preparing these
`
`10
`
`compounds. As an inventor on numerous patents I am also generally familiar with the patent
`
`prosecution process, including the requirement for an inventor DECLARATION and the duty to
`
`disclose information that is material to patentability that runs to each inventor.
`
`5.
`
`In the present continuation application (12/541,388) prosecution, now public as of
`
`01 April 2010, I recently noticed that a Preliminary Amendment was filed on 24 November
`
`15
`
`2009, which introduces New Matter into the claims. Specifically, while original claim 6 had no
`
`substituent at the 9-position of the pyrazino[2,1-c]triazine ring, new claim 43 that was added by
`
`the Preliminary Amendments encompasses new compounds not disclosed or otherwise taught in
`
`the original specification, and having an “Rd” radical at the 9-position of pyrazino[2,1-c]triazine
`
`ring (wherein “Rd” recites hydrogen or C1-6 alkyl) in the context of an adjacent “Ra” M
`
`20
`
`aryl group (see genus structures below). Significantly, while the original specification discloses
`
`(see Table 4; also see new claim 57 entered with the 24 November Preliminary Amendment) a
`
`few compounds having a methyl group (not “Rd”) at the 9—position, ALL five such structures
`
`(compounds 69, 78, 80, 83 and 111) comprise an adjacent “Ra” radical that is a monocyclic
`
`mofly. Likewise, compounds 81 and 82, having —CH20CHO and -CH20H group at the 9
`
`
`
`lI
`
`25
`
`position, respectively, comprise an adjacent “Ra” radical that is a monocyclic moiefl. The
`
`specification (including in View of the compounds in Table 4) has neither description nor
`
`explanation about the substituent “Rd” (there is no original teaching of “Rd is limited to
`
`hydrogen and C1.6 alkyl”), and particularly there is no teaching of “Rd” (of any type) in the
`
`context of an adjacent “Ra” bicyclic aryl group.
`
`
`
`
`
`M‘VXYO
`REX” in?
`
`3%
`
`32be an]m '
`“3’s.“
`\fkw/i
`kr
`
`Original Claim 6
`
`New claim 43
`
`6.
`
`Specifically, there is:
`
`(1) no written descriptive support in the original specification for an “Rd” group (wherein
`
`“Rd” recites hydrogen or C1_6 alkyl) as added and claimed by the 24 November 2009 Preliminary
`
`Amendment;
`
`(2) no enabling synthetic methods in the original specification that would reasonably
`
`teach one skilled in the art to synthesize compounds that contain such an “Rd” group, methyl or
`
`10
`
`otherwise, regardless of what the “Ra” group is;
`
`(3) no written descriptive support in the specification for an “Rd” group (wherein “Rd”
`
`recites hydrogen or C1.6 alkyl) in the context of an adjacent “Ra” bicyclic moiety;
`
`(4) no enabling synthetic methods in the original specification that would reasonably
`
`teach one skilled in the art to synthesize compounds that contain such an “Rd” group, methyl or
`
`15
`
`otherwise, in the context of an adjacent “Ra” bicyclic moiety; and
`
`(5) no enabling disclosure for the alleged stereochemistry at the 9—position of
`
`pyrazino[2,l—c]triazine ring of the Table 4 compounds.
`
`With respect to (1) and (3) above, the only groups disclosed at the 9-position of
`
`20
`
`pyrazino[2,l-c]triazine ring are methyl, —CH20CHO and -CH20H. The presently recited “Rd” is
`
`thus New Matter, irrespective of what the adjacent “Ra” substituent is. Furthermore, there are
`
`exclusively monocyclic groups at the “Ra” position of the compounds of 12/541,388 that contain
`
`a substituent at the 9—position, therefore, recitation of any “Rd” in the context of a bicyclic group
`
`3
`
`
`
`at Ra is New Matter. Specifically, all five such structures of Table 4 (compounds 69, 78, 80, 83
`
`and 111) comprise an adjacent “Ra” radical that is a monocyclic moiefl. Likewise, compounds
`
`81 and 82, having —CH20CHO and -CH20H group at the 9 position, respectively, comprise an
`
`adjacent “Ra” radical that is a monocyclic moiety.
`
`With respect to (2), (4) and (5) above, the placement of substituents at the 9-position of
`
`the pyrazino[2,l-c]triazine ring, the synthetic description in 12/541,388 is limited to the use of a
`
`bromoacetal resin, which is then reacted with an R2-substituted primary amine; that is, the
`
`described methods are limited to displacement of a polymer resin~bound primary acetal bromide
`
`by a primary amine, as depicted on pages 33 or 34 of the application as step 1. While this
`
`10
`
`procedure (employing a polymer resin-bound primary acetal bromide) may enable the synthesis
`
`of compounds where Rd = H, this synthetic route does not provide sufficient enablement for
`
`syntheses comprising displacement of a polymer resin-bound secondary acetal bromide, and in
`
`any event does not provide enablement for synthesis of stereospecific compounds, where Rd is
`
`not equal to H. As widely appreciated in the relevant art, a secondary acetal bromide is
`
`15
`
`substantially more hindered than a primary acetal bromide, and particularly in the case of a
`
`polymer resin-bound secondary acetal bromide, thereby precluding displacement of the hindered
`
`secondary amine by an R2-substituted primary amine. In fact, one would expect either no
`
`displacement reaction (see blocked step 1 below), or elimination of the bromide with the primary
`
`amine acting as a base (i.e., see elimination in scheme 1 below).
`Scheme 1
`
`/\
`
`0
`
`Pol-O
`
`3'
`
`Rd (not H)
`
`step I
`
`NHR2
`*>
`
`/\O
`
`Pol-O
`
`H
`N \
`
`R2
`
`Rd (not H)
`
`Wilden
`
`/\O
`
`'R
`
`d (e.g., -CH2 group)
`
`Pol-0
`
`20
`
`Additionally, the synthesis of a polymer-bound acetal bromide, would be expected to lead
`
`to an enantiomeric mixture of polymer-bound acetal bromide. Therefore, even if the step 1
`
`4
`
`
`
`reaction of above scheme 1 with “Rd” not H could be accomplished utilizing the procedures
`
`described in 12/541,3 88, any alleged product would n_ot be enantiomercally pure (NOTE: the
`
`12/541,3 88 specification is completely devoid of any X—ray structure or NOE NMR data, such
`
`that the stereochemistry of any alleged compounds with “Rd” not equal to H is
`
`unknown/ambiguous, and thus there is no enabling support for the stereochemistry of these
`structures, even ifthey could, for the sake of argument, be synthesized by the methods of
`
`12/541,388).
`
`Furthermore, the process depicted as step 2 on pages 33 and 34 of 12/541,388 would not
`
`be expected to proceed on solid phase resin (see scheme 2 below). Again, the highly hindered
`
`10
`
`nature of a secondary amine group (where “Rd” is not equal to H), even if Rd would be restricted
`
`to only methyl, and in articular if R2 was simultaneous] a bic clic heteroc cle, it would yet
`
`preclude a successfiil coupling reaction of this highly hindered secondary amine; that is, such
`
`coupling would not only be hindered by the highly hindered secondary amine, but also by the
`
`constraints imposed by solid phase resin, and further by a large bicyclic heterocycle as R2.
`Scheme 2
`
`/\O
`
`Pol-O
`
`H
`N\
`
`R2
`
`Rd (not H)
`
`step 2
`
`*>
`
`/\0 R2
`I
`N
`
`Pol-O
`
`R4
`
`NHFmoc
`
`Rd (not H) O
`
`O
`
`.
`
`NHFmoc
`
`HO
`
`15
`
`7.
`
`The presently claimed subgenus of newly added claim 43 is,
`
`therefore, not
`
`covered by the broader generic claims in the originally filed specification, and the complete
`
`absence in the original specification of a known or obvious process for making the claimed
`
`subgenus compounds overcomes any presumption that the compounds are obvious based on
`
`20
`
`relationships between their structures and those of the originally filed species and genera.
`
`Furthermore,
`
`the presently claimed subgenus of newly added claim 43 does not represent
`
`progressive “homologs” or “position isomers” of the originally filed genera compounds. Finally,
`
`
`
`even if for the sake of argument, the claim 43 subgenus were regarded as obvious, it nonetheless
`
`represents New Matter because of the lack of both written description (“Rd” in the context of
`
`bicyclic group) and enablement (e.g., no synthetic route).
`
`8.
`
`Accordingly, in satisfaction of the duty to disclose information that is material to
`
`patentability that runs to each inventor, as an original joint inventor, I hereby swear that the
`
`Preliminary Amendments filed on 24 November 2009 adds subject matter (New Matter) that
`
`extends beyond the original conception/invention, and moreover was not disclosed or otherwise
`
`taught in. the original specification, where there are @ species or genus structures and Q
`
`chemical syntheses whatsoever of any structures taught in the specification or original claims
`
`10
`
`having an “Rd” radical at the 9-position of the pyrazino[2,l—c]triazine ring (wherein “Rd” recites
`
`hydrogen or C1_6 alkyl) in the context of an adjacent “Ra” bicyclic aryl group. Moreover, the
`
`synthetic schemes that are provided are inadequate and thus nonenabling. Moreover, this would
`
`still true even if the “Rd” group were to be limited to a methyl group.
`
`9.
`
`Significantly, as discussed in detail above, the introduced non-H “Rd” radical not
`
`15
`
`only introduces a new chiral center, but also would spatially constrain a neighboring Ra bicyclic
`
`moiety to a much greater degree than a monocyclic moiety. Such amendments, therefore, cannot
`
`be presumed to be obvious modifications of the original genus, and even if they were so
`
`interpreted, there is still no written descriptive support for such New Matter, and insufficient
`
`enablement for such New Matter given the complete absence of disclosure of synthetic methods
`
`20
`
`or ability to product such compounds.
`
`In summary, the Preliminary Amendments filed on 24
`
`November 2009 go substantially beyond the original inventive conception/specification, and thus
`
`constitute New Matter under 35 U.S.C. Section 112, and moreover are not obvious extensions
`
`the original specification.
`
`10.
`
`In further satisfaction of the duty to disclose information that
`
`is material
`
`to
`
`25
`
`patentability that runs to each inventor and in view of the nature of the Preliminary Amendments
`
`filed on 24 November 2009, I believe that the lack of a Supplementag Declaration to support the
`
`Preliminary Amendment is material to the patentability of the presently claimed subject matter.
`
`The Preliminary amendments inappropriately expand the claimed subject matter by introducing
`
`6
`
`
`
`new compounds lacking support in the original specification, thus compromising the validity of
`
`any patent issuing on the present claims, and furthermore exposes the inventors to inequitable
`
`conduct if they were to consider executing such a Supplementary Declaration, which would yet
`
`further compromise the validity of any patent issuing on the present claims.
`
`11.
`
`In yet further satisfaction of the duty to disclose information that is material to
`
`patentabilig that runs to each inventor and in View of the nature of the Preliminary Amendments
`
`filed on 24 November 2009, I attach hereto a copy of PCT/JP2009/060718 filed on 05 June 2009,
`
`published as W02009148192 Al on 10 December 2009, and claiming priority to US.
`
`Provisional Patent Application Serial No. 61/059,607, filed 06 June 2008 (more that a year
`
`10
`
`before the filing date of 12/541,388, and almost a year and a half before the subject 24
`
`November 2009 Preliminary Amendment filed in 12/541,388). Additionally, attached is the
`
`International
`
`Search Report
`
`(ISR)
`
`of PCT/JP2009/060718, which
`
`together with
`
`PCT/JP2009/060718, is also material to the patentability of 12/541,388 as amended by the 24
`
`November 2009 Preliminary Amendment filed therein. PCT/JP2009/060718 not only anticipates
`
`15
`
`and obviates the presently claimed genus, but also provides, for the first time, a viable synthetic
`
`route for producing compounds (including stereochemically pure compounds) having,
`
`for
`
`example, a methyl group at the 9-position of pyrazino[2,1-c]triazine ring, and including in the
`
`context of an adjacent bicyclic aryl group.
`
`12.
`
`Specifically, in contrast to the above-described lack of enablement in 12/541,3 88
`
`20
`
`for a viable synthetic route for the claimed genus of newly added claim 43, PCT/JP2009/060718
`
`provides detailed synthetic methods (see, e.g., Figures 1, 2 and 3 of PCT/JP2009/060718) for
`
`producing its claimed chemical genera, comprising synthesis of the corresponding original
`
`amino acetal (where “Rd” is not equal to H) from, for example, an enantiomerically pure amino
`
`acid, followed by reductive amination to introduce the R2 substituent and subsequent coupling in
`
`25
`
`solution phase and not on polymer bound resin (e.g., see Scheme 3 below, which is my
`
`simplified summary of particular relevant PCT/JP2009/060718 synthetic methods).
`
`
`
`Scheme 3
`
`Rd (not H)
`
`Rd (not H)
`
`Rd (not H)
`—->
`
`“300
`
`NH2 —>
`
`H02C
`
`NH(Prot)
`
`H300
`
`H3CO
`
`H3CO
`
`NHR2
`
`Prot : protective group
`
`solution phase
`couphng
`
`Specifically, Figure 3 of PCT/JP2009/060718 discloses methods for producing “compound
`
`XVIII,” used in turn for producing “compound IX,” and where “Step 5” of Figure l of
`
`PCT/JP2009/060718 discloses a solution phase coupling of “compound IX” to “compound X.”
`
`These methods, therefore, not only provide for the first time an enabled synthetic route providing
`
`for provision of a “Rd” group that is not H, but also provides a Viable method for synthesizing
`
`enantiomerically pure product compounds.
`
`13.
`
`In summary therefore, not only is the 24 November 2009 amendment New
`
`10
`
`Matter, and lacking enablement, as described herein above, it is both anticipated and obviated by
`
`of PCT/JP2009/060718 filed on 05 June 2009, published as WO2009148192A1 on 10 December
`
`2009, and claiming priority to US. Provisional Patent Application Serial No. 61/059,607, filed
`
`06 June 2008 (more that a year before the filing date of 12/541,388, and almost a year and a half
`
`before the subject unsupported 24 November 2009 Preliminary Amendment filed in 12/541,388.
`
`15
`
`//
`
`//
`
`//
`
`//
`
`
`
`14.
`
`In summary,
`
`I further declare that all statements made herein of my own
`
`knowledge are true and that all statements made on information and belief are believed to be
`
`true, and that these statements are made with the knowledge that willful false statements and the
`
`like so made are punishable by fine or imprisonment, or both, under § 1001 of Title 18 of the
`
`United States Code, and may jeopardize the validity of the application or any patent issuing
`
`thereon.
`
`10
`
`
`
`Michael Kahn, Ph.D.
`
`12 May 2010
`
`
`
`APPENDIX A
`
`CURRICULUM VITAE
`
`Michael Kahn, Ph. D.
`
`Professor of Biochemistry and Molecular Biology
`Professor of Pharmacology and Pharmaceuticals
`Provost Professor of Medicine and Pharmacology
`1501 San Pablo, ZNI-533, Los Angeles, CA 90033
`
`Date of Birth:
`Place of Birth:
`Telephone:
`
`May 17, 1957
`New York, New York
`(323) 442-2063
`
`Education:
`
`1978 BA, Chemistry,
`
`Columbia University
`
`1983
`
`Ph.D., Chemistry
`
`Yale University
`
`Professional Experience:
`NIH Postdoctoral Fellow, Columbia University
`Research Associate, Hoffmann-LaRoche
`Assistant Professor, University of Illinois at Chicago
`Associate Professor, University of Illinios at Chicago
`Associate Professor, University of Washington
`Research Associate Professor, University of Washington
`Scientific Founder and Consultant, Molecumetics, Seattle, WA
`Chief Scientific Officer, Molecumetics, Seattle, WA
`Consultant to Asahi Chemical Corporation, Japan
`Senior Vice President, Molecumetics, Seattle, WA
`Consultant to ChoongWae Pharma Corporation, Korea
`Principal Investigator, PNRI, Seattle, WA
`Scientific Advisory Board Member, ITI, Seattle, WA
`Consultant to ITI, Seattle, WA
`Scientific Director, Institute for Chemical Genomics
`Member of SAB Presidio Pharmaceuticals, San Francisco, CA
`
`Member of SAB of Acucela, Seattle, WA
`
`Member of SAB of Prism Biolab, Mishima, Japan
`
`DWT 14632890v1 0067648-000003
`
`1 0
`
`1982-1984
`1984-1985
`1985-1988
`1988-1992
`1992-1995
`1995-present
`1992—1994
`1994-2000
`1995—2006
`1998-2000
`1999-2005
`2000-2004
`2001-2005
`2001-2005
`2004-2006
`2006—present
`
`2004-2008
`
`2006-present
`
`
`
`Editorial Boards
`Current Opinion in Anti—Inflammatory and Immunomodulatory
`Investigational Drugs
`Current Medicinal Chemistry Anti-Inflammatory and Anti-Allergy
`Agents
`
`Letters in Drug Design and Discovery
`Medicinal Chemistry Reviews Online
`
`
`Awards:
`
`Camille and Henry Dreyfus Distinguished Young Faculty Fellow
`Searle Scholar
`
`NSF Presidential Young Investigator
`American Cancer Society Junior Faculty Fellow
`Arnerican Cyanamid Faculty Award
`University Scholar — University of Illinois
`American Heart Association Established Investigator
`Camille and Henry Dreyfus Teacher Scholar
`
`Bibliography
`Journal Articles
`
`1999—2000
`
`2000-present
`
`2002-present
`2003-present
`
`1986—1991
`1986-1989
`
`1987-1992
`1987—1989
`1989
`1989
`1990-1995
`1991 -1 993
`
`1. Still, W. C., Kahn, M., and Mitra, A. 1978. Rapid Chromatographic Technique for
`Preparative Separations with Moderate Resolution. J Org. Chem. 51352923.
`
`2. Danishefsky, S., Zamboni, R., Kahn, M., and Etheredge, S. J. 1980. Total Synthesis of dl-
`
`Coriolin. J. Am. Chem. Soc. 1922097.
`'
`
`3. Kahn, M. 1980. Anionic Oxy-Cope Reaction of a Divinyl Cyclobutanol, Pleuromutilin
`Model Study. Tetrahedron Lett. A4547.
`
`4. Danishefsky, S., and Kahn, M. 1981. Regiospecific Michael Reactions to an Enedione.
`Tetrahedron Lett. 2:485.
`
`5. Danishefsky, S., and Kahn, M. 1981. Regiospecificity in the Diels Alder Reactions of an
`Enedione. Tetrahedron Lett. 2:489.
`
`6. Danishefsky, S., Zamboni, R., Kahn, M., and Etheredge, S. J. 1981. The Stereospecific
`Total Synthesis of dl-Coriolin and dl-Coriolin D. J. Am. Chem. Soc. 1031:3460.
`
`7. Danishefsky, S., Kahn, M., and Silvestri, M. 1982. Enol Carbonates: Weakly Nucleaophilic
`Precursors of Site-Specific Enolates. Tetrahedron Lett. 2:703.
`
`DWT l4632890v1 0067648-000003
`
`11
`
`
`
`8. Danishefsky, S., Kahn, M., and Silvestri, M. 1982. An Anomalous Mannich Reaction of
`Trimethylsilyl Enol Ether. Tetrahedron Lett. 2:1419.
`
`
`9. Stork, G., and Kahn, M. 1983. A Highly Stereospecific Osmium Tetroxide Catalyzed
`
`
`
`
`
`Hydroxylation of
`,
`-Unsaturated Esters. Tetrahedron Lett. £23951.
`
`10. Stork, G., and Kahn, M. 1985. Control of Ring Junction Stereochemistry Via Radical
`Cyclization. J. Am. Chem. Soc. 10—72500.
`
`[1. Kahn, M., and Devens, B. 1986. The Design and Synthesis of a Nonpeptide Mimic of an
`Immunosuppressing Peptide. Tetrahedron Lett. 22(40):4841-4844.
`
`12. Kahn, M., and Chen, B. 1987. Methodology for the Synthesis of Mimetics of Peptide
`
`Turns. Tetrahedron Lett. _2_8(15):1623-1626.
`
`10
`
`13. Kahn, M., Chen, B., and Zieske, P. 1987. The Design and Synthesis of a Nonpeptide
`Mimic of Erabutoxin. Heterocycles. 2_5:29-31.
`
`
`
`
`
`
`—
`
`14. Kahn, M., Lee, Y. W., Wilke, S., Chen, B., Fujita, K., and Johnson, M. 1988. The Design
`and Synthesis of Nonpeptide Mimetics of D-Turns. J. Mol. Recog. _1_:75.
`
`
`
`
`
`
`15
`
`-Tums: A
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`18. Olson, G., Voss, M.E., Hill, D.D., Kahn, M., Madison, V.S., and Cook, C. 1990. T_he
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`Design and Synthesis of a Protein :I-Tum Mimetic. J Am. Chem. Soc. £323.
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`19. Sato, M., and Kahn, M. 1990. A Convenient Preparation of l-Phenylsulfonyl-3-
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`20. Kahn, M., Chrusciel, A., Su, T., and Xuan, T. 1991. A Mechanistic Revision Concerning
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`21. Kahn, M, and Fujita, K. 1991. Enantiospecific Routes to 3,4 Disubstituted Azetidinones.
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`
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`22. Kahn, M., Nakanishi, H., Chrusciel, R.A., Fitzpatrick , D., and Johnson, ME. 1991.
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`23. Kahn, M., Nakanishi, H., Su, T., Lee, Y.H., and Johnson, ME. 1991. The Design and
`Synthesis of Nonpeptide Mimetics of Jaspamide. Int. J. Peptide Protein Res. $324634.
`
`24. Saragovi, H.U., Fitzpatrick, D., Raktabutr, A., Nakanishi, H., Kahn, M., and Greene, M.I.
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`Region. Science. @792-795.
`
`25. Chen, S., Chrusciel, R.A., Nakanishi, H., Raktabutr, A., Johnson, M.E., Sato, A., Weiner, D.,
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`26. Nakanishi, H., Chrusciel, R.A., Shen, R., Bertenshaw, S., Johnson, M.E., Rydel, T.J.,
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`
`27. Saragovi, H.U., Greene, M.I., Chrusciel, RA, and Kahn, M. 1992. Loops and Secondary
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`
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`28. Sato, M., Lee, J., Nakanishi, H., Johnson, M., Chrusciel, R.A., Kahn, M. 1992. Design,
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`Synthesis and Conformational Analysis of
`-Turn Peptide Mimetics of Bradykinin.
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`
`29. Shen, R., Priebe, C., Patel, C., Rubo, L., Sugasawara, R., and Kahn, M. 1992. An Approach
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`30. Gardner, B., Nakanishi, H., Kahn, M. 1993. Conformationally Constrained Nonpeptide El-
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`
`31. Kahn, M. 1993. Peptide Secondary Structure Mimetics: Recent Advances and Future
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`
`32. Nakanishi, H., Ramurthy, S., Raktabutr, A., Shen, R., and Kahn, M. 1993. Peptidomimetics
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`33. Sato, M., Kahn, M., Lin, Z., Johnson, M., Hayes, T. 1993. Design and Synthesis of
`Hypertrehalosemic Hormone Mimetics. Bioorg. Med. Chem. Lett. 3:1277-1282.
`
`
`34. Su, T., Nakanishi, H., Xue, L., Chen, B., Tuladhar, S., Johnson, M., and Kahn, M. 1993.
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`
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`35. Wu, T., Yee, V., Tulinsky, A., Chrusciel, R.A., Nakanishi, H., Shen, R., Priebe, C., Kahn,
`
`M. 1993. The Structure of a Designed Peptidomimetic Inhibitor Complex of E —Thrombin.
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`36. Olson, G.L., Bolin, D.R., Bonner, M.P., Bos, M., Cook, C.M., Fry, D.C., Graves, B.J.,
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`37. Johnson, M., Lin, 2., Padmanabhan, K., Tulinsky, A., and Kahn, M. 1994. Conformational
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`
`38. Ramurthy, S., Lee, M.S., Nakanishi, H., Shen, R., and Kahn, M. 1994. Peptidomimetic
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`
`39. Kim, H—O., Gardner, B., and Kahn, M. 1995. Acylation of Sterically Hindered Secondary
`Amines and Acyl Hydrazides. Tetrahedron Lett. fi(34)z6013-6016.
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`40. Kim, H-O., and Kahn, M. 1995. Approaches to the Acylation of Hindered Secondary
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`Amines. Synlett. 5 (Special Issue):549-551.
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`41. Lee, M.S., Gardner, B., Kahn, M., and Nakanishi, H. 1995. The Three—Dimensional
`Solution Structure of a Constrained Peptidomimetic in Water and in Chloroform.
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`42. O'Brien, J.S., Carson, G.S., Seo, H-C., Hiraiwa, M., Weiler, S., Tomich, J.M., Barranger,
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`
`43. Qabar, M.N., and Kahn, M. 1996. Synthesis of g S,S 2-3-Prolylazetidin-2-One: A Key
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`44. Qabar, M., Urban, J., Sia, G, Klein, M., and Kahn, M. 1996. Peptide Secondary Structure
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`
`45. Qabar, M., Urban, J., Sia, G, Klein, M., and Kahn, M. 1996. Pharmaceutical Applications
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`46. Urban, J., Qabar, M., Sia, G, Klein, M., Kahn, M. 1996. Sculpted Immunogens; B-Cell
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`
`47. Qabar, M., Urban, J., Kahn, M. 1997. A Facile Solution and Solid Phase Synthesis of
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`{Engpg EtO )2) Derivatives. Tetrahedron fl(3 2): 1 1 171-1 1 178.
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`48. Ferguson, M., Meara, J., Nakanishi, H., Lee, M., Kahn, M. 1997. The Development of
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`-Boc-amino -1-
`49. Kim, 0., Kahn, M. 1997. Short S nthesis of 38 68 9S -2-Oxo-3-
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`50. Blaskovich, M.A., Kahn, M. 1998. Sold-Phase Preparation of Dienes. J. Org. Chem.
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`
`51. Blaskovich, M.A., Kahn, M. 1998. Mild Conditions for oxazolidin—S-one Formation.
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`
`52. Blaskovich, M.A., Kahn, M. 1998. Polymer-Supported Acetylide Addition to
`
`dienal. Synthesis (7):965-966
`
`Hexa—2,4-
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`53. Ogbu, C.O., Qabar, M.N., Boatman, P.D., Urban, J., Meara, J.P., Ferguson, M.D., Tulinsky, J.,
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`54. Kim, H.O., Ogbu, C.O., Nelson, 8., Kahn, M. 1998. Convenient Synthesis of Electron
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`
`55. Eguchi, M., Ogbu, C., Boatman, D., Lee, M., Nakanishi, H., Cao, B., Tulinsky, A., Harker, L.,
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`56. Kim, H.O., Kahn, M. 1999. The Synthesis of Aminoazole Analogs of Lysine and Arginine:
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`
`57. Lee, M., Nakanishi, H., Kahn, M. 1999. Enlistment of Combinatorial Technigues in Drug
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`
`58. Boatman, D., Ogbu, C.O., Eguchi, M., Kim, H.O., Nakanishi, H., Cao, B., Shea, J.P., Kahn,
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`
`59. Eguchi, M., Lee, M., Nakanishi, H., Stasiak, M., Lovell, S., Kahn, M. 1999. Solid Phase
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`the i to i+3 Positions.
`.1 Am. Chem. Soc. 102:12204-12205.
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`60. Kim, H. 0., Nakanishi, H., Lee, M.S., Kahn, M. 2000. Design and Synthesis of Novel
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`61. Kim, H.—O., Kahn, M. 2000. A merger of rational drug design and combinatorial chemistry:
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`
`62. Kim, H.-O., Kahn, M. 2000. Recent developments in peptide secondary structure mimetics.
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`63. Fuchi, N., Doi, T., Harada, T., Urban, J., Cao, B., Kahn, M., Takahashi, T. 2001. T_he
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`64. Eguchi, M., Lee, M.S., Stasiak, M., Kahn, M. 2001. Solid-phase synthesis and solution
`structure of bicyclic [fi-turn peptidomimetics: diversity at the i position. Tetrahedron Lett. 42,
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`
`65. Misra—Press, A., McMillan, M., Cudaback, E., Khoury, D., Kozu, G., Thompson, P., Qabar,
`M., Ruan, F., Nguyen, M., Mathew, J., Vaisar, T., Nakanishi, H., Kahn, M. 2002.
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`
`66. Oh, S.W., Pae, C.I., Lee, D.K., Jones, E, Chiang, G.K.S., Kim, H.O., Moon, S.H., Cao, B.,
`Ogbu, C. Jeong, K.-W., Kahn, M, Chi, E.Y., Henderson, W.R., Jr. 2002. Tryptase inhibition
`blocks airway inflammation in a mouse asthma model. J Immunol, 168, 1992-2000.
`
`67. Fuchi, N., Doi, T., Cao, B., Kahn, M., Takahashi, T. 2002. The solid-phase parallel
`synthesis of fi-strand mimetic templates via 1,3-dipolar cycloaddition with resin-bou